Q13191A8K9S7B7WNM4Q13192Q13193Q3LIC0Q63Z43Q8IVC5CBLB_HUMANE3 ubiquitin-protein ligase CBL-B2.3.2.27Casitas B-lineage lymphoma proto-oncogene bRING finger protein 56RING-type E3 ubiquitin transferase CBL-BSH3-binding protein CBL-BSignal transduction protein CBL-BCBLBRNF56Nbla00127Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoCloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG; TRUNCATED 1 AND TRUNCATED 2)Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG)TISSUE SPECIFICITYINTERACTION WITH VAV1Cbl-b in Taiwan population.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG)Complete sequencing and characterization of 21,243 full-length human cDNAs.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG)The DNA sequence, annotation and analysis of human chromosome 3.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG)VARIANT LYS-584Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 543-982 (ISOFORM LONG)The full-ORF clone resource of the German cDNA consortium.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 857-982 (ISOFORM LONG)Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation.TISSUE SPECIFICITYMUTAGENESIS OF GLY-298; TYR-665 AND TYR-709INTERACTION WITH GRB2 AND CRKLPHOSPHORYLATION AT TYR-665 AND TYR-709FUNCTIONcbl-b inhibits epidermal growth factor receptor signaling.FUNCTIONPHOSPHORYLATIONINTERACTION WITH GRB2 AND PIK3R1Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells.FUNCTIONINTERACTION WITH PIK3R1MUTAGENESIS OF GLY-298 AND CYS-373Cbl-b-dependent coordinated degradation of the epidermal growth factor receptor signaling complex.UBIQUITINATIONMUTAGENESIS OF CYS-373Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells.FUNCTIONCIN85 participates in Cbl-b-mediated down-regulation of receptor tyrosine kinases.INTERACTION WITH SH3KBP1SUBCELLULAR LOCATIONCbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation.FUNCTIONCATALYTIC ACTIVITYCbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b.INTERACTION WITH UBIQUITINATED PROTEINSMUTAGENESIS OF 943-GLY-TYR-944 AND LEU-967Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]A quantitative atlas of mitotic phosphorylation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-521; SER-525 AND SER-529IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation.PHOSPHORYLATION AT SER-282The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme.FUNCTION AS E3 UBIQUITIN-PROTEIN LIGASECATALYTIC ACTIVITYPHOSPHORYLATION AT TYR-363MUTAGENESIS OF TYR-363IFT20 modulates ciliary PDGFRalpha signaling by regulating the stability of Cbl E3 ubiquitin ligases.INDUCTIONINTERACTION WITH IFT20 AND CBLCbl promotes clustering of endocytic adaptor proteins.X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 899-914 IN COMPLEXES WITH SH3KBP1 AND ARHGEF7MUTAGENESIS OF ARG-904 AND ARG-911SUBUNITAtypical polyproline recognition by the CMS N-terminal Src homology 3 domain.X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 902-912 IN COMPLEX WITH CD2APMUTAGENESIS OF ARG-904; LYS-907 AND ARG-911SUBUNITStructural basis for ubiquitin-mediated dimerization and activation of the ubiquitin protein ligase Cbl-b.X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 924-973 IN COMPLEX WITH UBIQUITINSTRUCTURE BY NMR OF 924-973TYROSINE PHOSPHORYLATIONMUTAGENESIS OF ALA-937; MET-940; PHE-946 AND ILE-966Solution structure of RSGI RUH-065, a UBA domain from human cDNA.STRUCTURE BY NMR OF 931-970Crystal structure of Cbl-b TKB domain in complex with EGFR pY1069 peptide.X-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS) OF 38-344 IN COMPLEX WITH PHOSPHO-EGFR PEPTIDEINTERACTION WITH EGFRHETERODIMERE3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.Protein modification; protein ubiquitination.Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL (PubMed:29237719). Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). Interacts with IFT20 (PubMed:29237719).Q13191Q8IZP0false2Q13191Q9ULH1false2Q13191Q9Y5K6false11Q13191P46108false4Q13191P46109false4Q13191O75190false3Q13191Q01658false3Q13191P35637false3Q13191P06241-3false4Q13191O76003false3Q13191Q9H8Y8false8Q13191P62993false26Q13191Q00403false3Q13191Q9Y5Q9false3Q13191Q5S007false4Q13191P16333false4Q13191O43639false8Q13191P35240-4false3Q13191P55345false3Q13191Q13882false3Q13191Q96B97false22Q13191P00441false3Q13191O94875-10false3Q13191Q6NUL7false3Q13191Q13148false6Q13191P57075-2false3Q13191Q8TF42false6Q13191Q9UKW4false3Q13191O14972false3Q13191P07947false3Q13191-1Q9BXL7false4Q13191-1Q96B97-1false3Q13191-1P62837false2Q13191-1O55043true2CytoplasmUpon EGF stimulation, associates with endocytic vesicles.Q13191-1LongQ13191-2Truncated 1Q13191-3Truncated 2Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level).By serum starvation.The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.The UBA domain interacts with poly-ubiquitinated proteins.Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.This protein has one functional calcium-binding site.Truncated C-terminus.Probable cloning artifact.3D-structureAlternative splicingCalciumCytoplasmMetal-bindingPhosphoproteinReference proteomeRepeatTransferaseUbl conjugationUbl conjugation pathwayZincZinc-fingerCa(2+)Ca(2+)Ca(2+)Ca(2+)Ca(2+)4-O-phospho-L-tyrosineDVFDTYRIRKNDGEYECAYFYFRAKARAAEMAGYAQFAIELAGSRCMANSMNGRNPGGRGGNPRKGRILGIIDAIQDAVGPPKQAAADRRTVEKTWKLMDKVVRLCQNPKLQLKNSPPYILDILPDTYQHLRLILSKYDDNQKLAQLSENEYFKIYIDSLMKKSKRAIRLFKEGKERMYEEQSQDRRNLTKLSLIFSHMLAEIKAIFPNGQFQGDNFRITKADAAEFWRKFFGDKTIVPWKVFRQCLHEVHQISSGLEAMALKSTIDLTCNDYISVFEFDIFTRLFQPWGSILRNWNFLAVTHPGYMAFLTYDEVKARLQKYSTKPGSYIFRLSCTRLGQWAIGYVTGDGNILQTIPHNKPLFQALIDGSREGFYLYPDGRSYNPDLTGLCEPTPHDHIKVTQEQYELYCEMGSTFQLCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQGCPFCRCEIKGTEPIIVDPFDPRDEGSRCCSIIDPFGMPMLDLDDDDDREESLMMNRLANVRKCTDRQNSPVTSPGSSPLAQRRKPQPDPLQIPHLSLPPVPPRLDLIQKGIVRSPCGSPTGSPKSSPCMVRKQDKPLPAPPPPLRDPPPPPPERPPPIPPDNRLSRHIHHVESVPSRDPPMPLEAWCPRDVFGTNQLVGCRLLGEGSPKPGITASSNVNGRHSRVGSDPVLMRKHRRHDLPLEGAKVFSNGHLGSEEYDVPPRLSPPPPVTTLLPSIKCTGPLANSLSEKTRDPVEEDDDEYKIPSSHPVSLNSQPSHCHNVKPPVRSCDNGHCMLNGTHGPSSEKKSNIPDLSIYLKGDVFDSASDPVPLPPARPPTRDNPKHGSSLNRTPSDYDLLIPPLGEDAFDALPPSLPPPPPPARHSLIEHSKPPGSSSRPSSGQDLFLLPSDPFVDLASGQVPLPPARRLPGENVKTNRTSQDYDQLPSCSDGSQAPARPPKPRPRRTAPEIHHRKPHGPEAALENVDAKIAKLMGEGYAFEEVKRALEIAQNNVEVARSILREFAFPPPVSPRLNL
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